CLINICAL IMMUNOLOGY
Contribution of the STAT4 rs7574865 gene polymorphism to the susceptibility to autoimmune thyroiditis in healthy Turk population and psoriatic subgroups
Submission date: 2015-06-08
Final revision date: 2015-07-03
Acceptance date: 2015-07-06
Publication date: 2016-01-15
Cent Eur J Immunol 2015;40(4):437-441
KEYWORDS
psoriasispolymorphismSignal transducer and activator of transcription 4 (STAT4)autoimmune diseaseJAK / STATautoimmune thyroiditisrs7574865
ABSTRACT
Introduction: STAT4 is an important transcription factor that activates gene transcription as a response to cytokines. Recently, the influence of STAT4 gene on autoimmune disease has been widely studied in many different immune-related diseases. Autoimmune, metabolic and cardiovascular disorders are more common in psoriatic patients. STAT4 may be a unique gene that switches on in autoimmune-related thyroid disease in psoriatic patients.
The aim of the study: To explore the association of a STAT4 rs7574865 polymorphism to autoimmune thyroid diseases in the general Turkish population and psoriatic subgroups.
Material and methods: A total of 132 psoriatic patients and 118 non-psoriatic volunteers were genotyped for STAT4 rs7574865 using real time PCR. Twenty-four of the psoriatic patients and 15 of the non-psoriatic volunteers have autoimmune-related thyroid diseases.
Results: The prevalence of the T allele [OR = 4.37; 95% CI: 1.05-19; p = 0.03] of the STAT4 rs7574865 was higher in individuals with autoimmune-related thyroid diseases among the all non-psoriatic volunteers. The volunteers with autoimmune-related thyroid diseases has an increased allele positivity and carriers having at least one of the risk allele was significantly higher than in counterparts with a GG wild genotype [ORGT/TT vs. GG: 1.73; 95% CI: 0.09-32; p = 0.03]. Yet, there was no evidence of an association between rs7574865 and autoimmune-related thyroid disease in psoriatic patients.
Conclusions: The STAT4 rs7574865 polymorphism increases autoimmune-related thyroid disease susceptibility among the general population but not in psoriatic patients.
The aim of the study: To explore the association of a STAT4 rs7574865 polymorphism to autoimmune thyroid diseases in the general Turkish population and psoriatic subgroups.
Material and methods: A total of 132 psoriatic patients and 118 non-psoriatic volunteers were genotyped for STAT4 rs7574865 using real time PCR. Twenty-four of the psoriatic patients and 15 of the non-psoriatic volunteers have autoimmune-related thyroid diseases.
Results: The prevalence of the T allele [OR = 4.37; 95% CI: 1.05-19; p = 0.03] of the STAT4 rs7574865 was higher in individuals with autoimmune-related thyroid diseases among the all non-psoriatic volunteers. The volunteers with autoimmune-related thyroid diseases has an increased allele positivity and carriers having at least one of the risk allele was significantly higher than in counterparts with a GG wild genotype [ORGT/TT vs. GG: 1.73; 95% CI: 0.09-32; p = 0.03]. Yet, there was no evidence of an association between rs7574865 and autoimmune-related thyroid disease in psoriatic patients.
Conclusions: The STAT4 rs7574865 polymorphism increases autoimmune-related thyroid disease susceptibility among the general population but not in psoriatic patients.
REFERENCES (20)
1.
Thierfelder WE, van Deursen JM, Yamamoto K, et al. (1996): Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382: 171-174.
2.
Wurster AL, Tanaka T, Grusby MJ (2000): The biology of Stat4 and Stat6. Oncogene 19: 2577-2584.
3.
Good SR, Thieu VT, Mathur AN, et al. (2009): Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming. J Immunol 183: 3839-3847.
4.
Liang Y, Pan HF, Ye DQ (2014): Therapeutic potential of STAT4 in autoimmunity. Expert Opin Ther Targets 18: 945-960.
5.
Yan N, Meng S, Zhou J, et al. (2014): Association between STAT4 gene polymorphisms and autoimmune thyroid diseases in a Chinese population. Int J Mol Sci 15: 12280-12293.
6.
Chomiczewska-Skóra D, Trznadel-Grodzka E, Rotsztejn H (2013): Psoriasis as a disease associated with the immune system disorders. Centr Eur J Immunol 38: 129-133.
7.
Wojas-Pelc A, Ciszek M, Kurnyta M, Marcinkiewicz J (2006): Cytokine network in psoriasis Cross-talk between keratinocytes and cells. Centr Eur J Immunol 31: 111-116.
8.
Boivin N, Baillargeon J, Doss PM, et al. (2015): Interferon- suppresses murine Th1 cell function in the absence of antigen-presenting cells. PLoS One 10: e0124802.
9.
Avouac J, Fürnrohr BG, Tomcik M, et al. (2011): Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis. Arthritis Rheum 63: 800-809.
10.
Menke J, Bork T, Kutska B, et al. (2011): Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in mice. Kidney Int 79: 452-463.
11.
Fan ZD, Wang FF, Huang H, et al. (2015): STAT4 rs7574865 G/T and PTPN22 rs2488457 G/C polymorphisms influence the risk of developing juvenile idiopathic arthritis in Han Chinese patients. PLoS One 10: e0117389.
12.
Holz A, Bot A, Coon B, et al. (1999): Disruption of the STAT4 signaling pathway protects from autoimmune diabetes while retaining antiviral immune competence. J Immunol 163: 5374-5382.
13.
Boyton RJ, Davies S, Marden C, et al. (2005): Stat4-null non-obese diabetic mice: protection from diabetes and experimental allergic encephalomyelitis, but with concomitant epitope spread. Int Immunol 17: 1157-1165.
14.
Cetkovic-Cvrlje M, Uckun FM (2005): Effect of targeted disruption of signal transducer and activator of transcription Stat4 and Stat6 genes on the autoimmune diabetes development induced by multiple low doses of streptozotocin. Clin Immunol 114: 299-306.
15.
Dobrian AD, Galkina EV, Ma Q, et al. (2013): STAT4 deficiency reduces obesity-induced insulin resistance and adipose tissue inflammation. Diabetes 62: 4109-4121.
16.
Ben Hamad M, Cornelis F, Mbarek H, et al. (2011): Signal transducer and activator of transcription and the risk of rheumatoid arthritis and thyroid autoimmune disorders. Clin Exp Rheumatol 29: 269-274.
17.
Gourh P, Agarwal SK, Divecha D, et al. (2009): Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines. Arthritis Rheum 60: 3794-3806.
18.
Liang YL, Wu H, Shen X, et al. (2012): Association of STAT4 rs7574865 polymorphism with autoimmune diseases: a meta-analysis. Mol Biol Rep 39: 8873-8882.
19.
Land KJ, Gudapati P, Kaplan MH, Seetharamaiah GS (2006): Differential requirement of signal transducer and activator of transcription-4 (Stat4) and Stat6 in a thyrotropin receptor-289-adenovirus-induced model of Graves’ hyperthyroidism. Endocrinology 147: 111-119.
20.
Park Y, Lee HS, Park Y, et al. (2011): Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population. Diabetes Metab Res Rev 27: 867-871.
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